APPENDIX-I



APPENDIX-I

6. BRIEF RESUME OF THE INTENDED WORK:

APPENDIX-IA

6.1 NEED FOR THE STUDY

Asphyxia is a common occurrence during the neonatal period. Although it is a major contributor to neonatal morbidity and mortality, the diagnosis and evaluation of asphyxia can be problematic.

Neonatal asphyxia is a common neonatal problem and contributes significantly to neonatal morbidity and mortality. Globally, hypoxia of the newborn (birth asphyxia) or the fetus ("fresh stillbirth") is estimated to account for 23% of the 4 million neonatal deaths and 26% of the 3.2 million stillbirths each year1. An estimated 1 million children who survive birth asphyxia live with chronic neurodevelopmental morbidities, including cerebral palsy, mental retardation, and learning disabilities. In India, between 250,000 to 350,000 infants die each year due to birth asphyxia, mostly within the first three days of life. In addition, ante-partum and intra-partum asphyxia contributes to as many as 300,000 to 400,000 stillbirths. In India, 8.4% of inborn babies have a one minute Apgar score less than 7 and 1.4% suffer from hypoxic ischemic encephalopathy (HIE)2 . Accurate estimates of the proportion of neonatal mortality attributable to birth asphyxia are limited by the lack of a consistent definition for use in community-based settings and the absence of vital registration in communities where the majority of neonatal deaths occur.

Only a third of deliveries in India are institutional and many asphyxiated babies are brought late to hospitals. The signs of asphyxial injury are nonspecific and overlap with other illnesses. In the absence of perinatal records, it is difficult to retrospectively diagnose neonatal asphyxia.

Although asphyxia is associated with multiple organ injuries, especially with adverse neurological outcomes, management still focuses on supportive care. So, if the adverse effects of hypoxia on the newborn are considered, there is a need to identify infants who will be at high risk for hypoxic ischemic encephalopathy and early neonatal death as a consequence of neonatal hypoxia. A variety of markers have been examined to identify neonatal hypoxia including electronic fetal heart monitoring, low Apgar scores, cord pH, electroencephalograms, computed tomography (CT) and magnetic resonance imaging (MRI) scans and Doppler flow studies. Supplementary methods for diagnosis and prediction of antenatal and non-acidotic prolonged asphyxia are lacking.

Neonatal asphyxia may result in adverse effects on all major body systems. Many of these complications are potentially fatal. In a term infant with perinatal asphyxia renal, neurologic, cardiac and lung dysfunction occurs in 50%, 28%, 25% and 23% cases respectively. The extent of multi-organ dysfunction determines the early outcome of an asphyxiated neonate with either the neonate succumbing as a consequence of organ damage or recovering completely. Generally there are no long term sequelae associated with these organ system derangements. Hypoxic ischemic encephalopathy (HIE) refers to the CNS dysfunction associated with perinatal asphyxia. HIE is foremost concern in an asphyxiated neonate because contrary to other system derangements this has the potential to cause serious long term neuromotor sequelae among survivors.

The neuro-developmental delay cannot be assessed with currently used diagnostic methods in the patients with perinatal asphyxia or Hypoxic-Ischemic Encephalopathy(HIE))3,4,5

Neonatal asphyxia causes neurological morbidity and mortality in full-term infants. Despite the increasing understanding of the mechanisms leading to and resulting from neonatal asphyxia, early determination of brain damage following hypoxic-ischemic events still remains one of the hardest problems in neonatal care.6,7,8

Neonatal hypoxia is one of the leading causes of neonatal mortality in developing countries. Birth asphyxia is an important cause of static developmental and neurological handicap both in term and preterm infants (in 3 to 13% of infants with cerebral palsy (CP) have evidence of intrapartum asphyxia) 9

Brief hypoxia impairs cerebral oxidative metabolism leading to an anaerobic glycolysis to generate ATP. During anerobic conditions one molecule of glucose yields only 2 molecules ofATP as opposed to producing 38 molecules of ATP during

aerobic conditions10-18

During prolonged hypoxia, cardiac output falls, cerebral blood flow (CBF) is compromised and a combined hypoxic-ischemic insult produces further failure of

oxidative phosphorylation and ATP production, sufficient to cause cellular damage10-18

Lack of ATP and increase excitotoxic cellular damage leads to an accumulation of adenosine diphosphate (ADP) and adenosine monophosphate (AMP), which is then catabolized to adenosine, inosine and hypoxanthine10-18

If there is uninterrupted tissue hypoxia and there is also reperfusion injury, hypoxanthine is oxidized to xanthine and uric acid in presence of xanthine oxidase leading to an increase in uric acid production, which come out in blood from tissues and excreted in urine.10-18

In the reoxygenation period, radicals are produced parallel to uric acid formation,

which may be linked to the severity of perinatal asphyxia.10-18

Urinary uric acid and creatnine in 24 hours urine sample is 250-750 mg/lit/24hrs and 1 to 2 gms/lit/24hrs respectively.33,34

Uric acid level in spot urine of normal preterm AGA (appropriate for gestational age) babies in day one of their life. was 36.50 +/- 5.99 mg/dl in normal preterm neonates as compared to 18.40 +/- 0.45 mg/dl in normal term babies.33,34

Though there are more and more studies and understanding of the

mechanisms leading to birth asphyxia, early determination of tissue damages due to birth asphyxia are still lackin

This study is to evaluate the utility of urinary uric acid to creatinine ratio (UA/Cr ratio) within 24 hours of birth as non-invasive, easy, cheap and at the same time early

biochemical means of asphyxia diagnosis and also to find out whether Apgar score is still an important tool for birth asphyxia diagnosis and its severity calculation19-20

APPENDIX –IB

1. REVIEW OF LITERATURE:

Birth asphyxia is the most common and important cause of preventable cerebral injury occurring in the neonatal period, but although asphyxia at birth is a commonly made diagnosis, there is generally no accepted definition for it. The term is used to imply an abnormal process and one that, if untreated, may cause permanent injury. Asphyxia, at a pathophysiological level, is the simultaneous combination of both hypoxia and hypoperfusion, which impairs tissue gas exchange leading to tissue acidosis.

There is no unanimity or consensus regarding the definition of birth asphyxia and various workers have used different definitions making it difficult to ascertain the incidence of asphyxia. The World Health Organization has defined birth asphyxia as “failure to initiate and sustain breathing at birth” and based on Apgar score as an Apgar score of ................
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